Michael L. Pearl

Incontinence following rupture of the anal sphincter during delivery

Objective: To determine the frequency with which patients report incontinence of flatus or stool after rupture of the anal sphincter during delivery. Methods: A chart review and telephone interview were conducted with 70 primiparas, 35 of whom had rupture of the anal sphincter at delivery and 35 of whom did not. All were contacted 9‐12 months postpartum and questioned about the development of incontinence of gas or liquid or formed stool, persistent dyspareunia, and perineal pain. Results: Incontinence of gas was reported by six women (17%) in the rupture group and one (3%) in the control group (P < .05). The incidences of incontinence of stool, both liquid and solid, dyspareunia, and persistent perineal pain were similar between the groups. Conclusion: Incontinence of flatus was reported six times more often by women who experienced a third‐ or fourth‐degree perineal laceration than by those without anal sphincter rupture. (Obstet Gynecol 1993;82:527‐31)

Laparoscopic injury of abdominal wall blood vessels: A report of three cases

Background:Operative laparoscopy is being used for an increasing number of applications. Many of these innovative techniques require the insertion of large trocars through the anterior abdominal wall at points lateral to the midline. Because of the rich vascular supply of the anterior abdominal wall

Synchronous dual primary ovarian and endometrial carcinomas

OBJECTIVES: The synchronous occurrence of carcinoma confined to the ovary and endometrium presents a diagnostic and therapeutic dilemma. These tumors have been variously staged as FIGO Stage IIA ovarian carcinoma, Stage III endometrial carcinoma, or synchronous dual primary carcinomas. Accumulating evidence suggests such patients have a favorable outcome. This retrospective study was undertaken to review our experience with these fascinating tumors. METHODS: The clinical records and the pathologic findings of 16 patients with synchronous dual primary ovarian and endometrial carcinomas were reviewed. RESULTS: The median age was 51 years. Abnormal uterine bleeding was the most common presenting symptom (70%). All patients had Stage I ovarian and endometrial carcinomas. Fourteen patients (88%) had endometrioid carcinoma in both sites, while two patients (12%) had dissimilar histology. For 15 patients (94%), the grade of both tumors was identical. Only three (19%) patients had myometrial invasion, with less than 50% involvement in each case. All patients underwent surgical staging, 11 (70%) of whom received adjuvant radiation or chemotherapy. The five patients treated with surgery alone had Grade 1 endometrioid tumors. The only relapse occurred in a patient with a clear cell component in both sites. No patient has died of disease. CONCLUSIONS: Patients with synchronous dual primary carcinomas appear to have a more favorable prognosis than that expected with Stage IIA ovarian or Stage III endometrial carcinoma (100% vs. 63% or 42% survival at 3 years, respectively). The excellent survival for patients with Grade 1 dual endometrioid tumors treated with surgery alone suggests that adjuvant therapy may not be necessary for this sub‐group.

Predicting drug interactions in vivo from experiments in vitro : Human studies with paclitaxel and ketoconazole

This study was performed to evaluate whether concomitant treatment with ketoconazole could reduce the clearance of paclitaxel given to ovarian cancer patients. Paclitaxel, 175 mg/m2, was given as a 3-hour continuous intravenous infusion and repeated every 21 days. Initially, ketoconazole, 100 to 1600 mg, was given as a single oral dose 3 hours after paclitaxel. Later, ketoconazole, 200 mg, was given perorally 3 hours before paclitaxel. Plasma drug concentrations were measured by high-pressure liquid chromatography (HPLC), and cytochrome P450 3A (CYP3A) activity was measured with the erythromycin breath test (ERMBT). Ketoconazole did not alter plasma concentrations of paclitaxel or its principal metabolite, 6 alpha-hydroxypaclitaxel. Although there was marked inter- and intrapatient variability in ketoconazole pharmacokinetics, peak plasma concentrations in all but one course were below the 50% inhibitory concentration (IC50) point determined for inhibition of paclitaxel metabolism in vitro. Therefore, paclitaxel and ketoconazole can be coadministered safely without dose adjustments. There was no correlation between ERMBT measurements and serial plasma concentrations of paclitaxel. The erythromycin breath-test measurements did correlate with the corresponding ketoconazole plasma concentrations. The erythromycin breath test is a valuable tool for measuring instantaneous CYP3A activity in vivo. This clinical study confirms the results of prior studies with human-derived materials in vitro, reinforcing the notion that such studies are useful predictors of drug pharmacokinetics and interactions in vivo.

cAMP and PMA enhance the effects of IGF-I in the proliferation of endometrial adenocarcinoma cell line HEC-1-A by acting at the G1 phase of the cell cycle

The present study was undertaken to determine whether endometrial cancer cell line HEC‐1‐A differ from nontransformed cells, in that the cAMP and protein kinase C pathways may enhance IGF‐I effects in mitogenesis by acting at the G1 phase of the cell cycle instead of G0. Immunofluorescence staining of HEC‐1‐A cells using the proliferating cell nuclear antigen (PCNA) monoclonal antibody and flow cytometric analysis determined that HEC‐1‐A cells do not enter the G0 phase of the cell cycle when incubated in a serum‐free medium. Approximately 51% of the cells were in G1, 12% were in S and 37% in G2 phase of the cell cycle prior to treatment. Forskolin and phorbol‐12‐myristate 13‐acetate (PMA) were used to stimulate cAMP production and protein kinase C activity, respectively. IGF‐I, forskolin and PMA each increased (P <0.01) [3H]‐thymidine incorporation in a dose and time dependent manner. The interaction of forskolin and PMA with IGF‐I was then determined. Cells preincubated with forskolin or PMA followed by incubation with IFG‐I incorporated significantly more (P <0.01) [3H]‐thymidine into DNA than controls or any treatment alone. It is concluded that forskolin and, to a lesser extent, PMA exert their effect at the G1 phase of the cycle to enhance IGF‐I effects in cell proliferation.

Absence of cumulative bone marrow suppression in heavily pretreated ovarian cancer patients undergoing salvage chemotherapy with paclitaxel

This retrospective study was undertaken to investigate whether paclitaxel was associated with cumulative bone marrow toxicity in patients undergoing salvage chemotherapy for refractory ovarian cancer. Seventy-seven patients were treated with paclitaxel 135 mg/m2 every 21 days, with granulocyte-colony-stimulating factor (G-CSF) support as necessary according to standard criteria. The mean white blood cell nadir was significantly higher and the incidence of severe leukopenia (Gynecologic Oncology Group grade 3-4) significantly lower after ten cycles than after the first cycle for the entire study population (3.4 vs. 1.6 x 10(3)/mm3 and 29 vs. 77%, respectively) and the patients who received G-CSF (3.5 vs. 1.4 x 10(3)/mm3 and 33 vs. 89%, respectively), but did not differ significantly for the patients who did not require G-CSF (2.9 vs. 2.5 x 10(3)/mm3 and 40 vs. 59%, respectively). The mean hematocrit and platelet nadirs, as well as the incidence of severe anemia and thrombocytopenia, did not differ significantly after ten cycles from those after the first cycle for the entire study population and both subgroups. Thirty-two (42%) patients received G-CSF, each initiated within four cycles. The indications for initiating G-CSF support were febrile leukopenia (53%) and treatment delay (47%). The average duration of G-CSF support was 4.6 days, and did not increase significantly as the number of paclitaxel cycles increased. We conclude that paclitaxel was not associated with cumulative bone marrow toxicity in patients undergoing salvage chemotherapy for refractory ovarian cancer.